Polynucleotides and polypeptide sequences involved in the process of bone remodeling

Abstract

This invention relates, in part, to unique and newly identified genetic polynucleotides involved in the process of bone remodeling; variants and derivatives of the polynucleotides and corresponding polypeptides; uses of the polynucleotides, polypeptides, variants and derivatives; and methods and compositions for the amelioration of symptoms caused by bone remodeling disorders. Disclosed in particular are, the isolation and identification of polynucleotides, polypeptides, variants and derivatives involved in osteoclast activity, validation of the identified polynucleotides for their potential as therapeutic targets and use of the polynucleotides, polypeptides, variants and derivatives for the amelioration of disease states and research purposes.

1 - 55 . (canceled) 
     
     
         56 . A method for inhibiting bone resorption comprising administering to a subject in need an antibody or an antigen binding fragment capable of specific binding to a polypeptide having at least 67% sequence similarity with SEQ ID NO.:153. 
     
     
         57 . The method of  claim 56 , wherein the polypeptide is capable of inducing differentiation of osteoclasts. 
     
     
         58 . The method of  claim 56 , wherein the polypeptide has a sequence at least 80% identical, at least 90% identical or at least 95% identical to SEQ ID NO.:153 or SEQ ID NO.:93. 
     
     
         59 . The method of  claim 56 , wherein the polypeptide has a sequence identical to SEQ ID NO.:153 or SEQ ID NO.:93. 
     
     
         60 . The method of  claim 56 , wherein the antibody or antigen binding fragment is capable of impairing an activity of the polypeptide in osteoclast precursor cells or in osteoclasts. 
     
     
         61 . The method of  claim 56 , wherein the antibody or antigen binding fragment inhibits osteoclast differentiation. 
     
     
         62 . The method of  claim 56 , wherein the antibody is selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a chimeric antibody, a humanized antibody and a human antibody. 
     
     
         63 . The method of  claim 56 , wherein the antigen binding fragment is a FV, a Fab, a Fab′ or a (Fab′) 2 . 
     
     
         64 . The method of  claim 56 , wherein the antibody or antigen binding fragment is administered in combination with a drug or an hormone. 
     
     
         65 . The method of  claim 64 , wherein the drug is an antiresorptive drug or a drug increasing bone mineral density. 
     
     
         66 . The method of  claim 56 , wherein the antibody or antigen binding fragment is conjugated with a therapeutic agent. 
     
     
         67 . The method of  claim 56 , wherein the subject in need suffers from a bone remodelling disorder. 
     
     
         68 . The method of  claim 67 , wherein the bone remodelling disorder is associated with a decrease in bone mass. 
     
     
         69 . The method of  claim 67 , wherein the bone remodelling disorder is selected from the group consisting of osteoporosis, osteopenia, osteomalacia, hyperparathyroidism, hyperthyroidism, hypogonadism, thyrotoxicosis, systemic mastocytosis, adult hypophosphatasia, hyperadrenocorticism, osteogenesis imperfecta, Paget's disease, Cushing's disease/syndrome, Tumer syndrome, Gaucher disease, Ehlers-Danlos syndrome, Marfan's syndrome, Menkes' syndrome, Fanconi's syndrome, multiple myeloma, hypercalcemia, hypocalcemia, arthritides, periodontal disease, rickets, fibrogenesis imperfecta ossium, osteosclerotic disorders such as pycnodysostosis and damage caused by macrophage-mediated inflammatory processes. 
     
     
         70 . A pharmaceutical composition comprising:
 a. An antibody or an antigen binding fragment capable of specific binding to a polypeptide having at least 67% sequence similarity with SEQ ID NO.:153 and of impairing an activity of the polypeptide in osteoclast precursor cells or in osteoclasts and;   b. A pharmaceutically acceptable carrier.   
     
     
         71 . The pharmaceutical composition of  claim 70 , wherein the polypeptide has a sequence at least 80% identical, at least 90% identical or at least 95% identical to SEQ ID NO.:153 or SEQ ID NO.:93. 
     
     
         72 . The pharmaceutical composition of  claim 70 , wherein the polypeptide has a sequence identical to SEQ ID NO.:153 or SEQ ID NO.:93. 
     
     
         73 . The pharmaceutical composition of  claim 70 , wherein the antibody or antigen binding fragment inhibits osteoclast differentiation. 
     
     
         74 . The pharmaceutical composition of  claim 70 , wherein the antibody is selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a chimeric antibody, a humanized antibody and a human antibody. 
     
     
         75 . The pharmaceutical composition of  claim 70 , wherein the antigen binding fragment is a FV, a Fab, a Fab′ or a (Fab′) 2 . 
     
     
         76 . The pharmaceutical composition of  claim 70 , further comprising a drug or an hormone. 
     
     
         77 . The pharmaceutical composition of  claim 76 , wherein the drug is an antiresorptive drug or a drug increasing bone mineral density. 
     
     
         78 . The pharmaceutical composition of  claim 70 , wherein the antibody or antigen binding fragment is conjugated with a therapeutic agent.